Association of tumor genomic factors and efficacy for metastasis-directed stereotactic body radiotherapy for oligometastatic colorectal cancer

Purpose/objective(s): To report tumor genomic factors associated with overall survival (OS) and local failure (LF) for patients with colorectal cancer (CRC) who received metastasis-directed stereotactic body radiation therapy (SBRT).

Materials/methods: This was a retrospective review of patients with CRC who received metastasis-directed SBRT. Tumor genomic alterations were identified through KRAS, BRAF, or a 50-gene next generation sequencing panel. OS and LF were estimated using Kaplan-Meier and competing-risk methods.

Results: Eighty-five patients and 109 lesions were treated between 2008 and 2018. The median patient follow-up was 50 months (IQR: 28-107). The median and 5-year OS was 34 months and 26% (95% CI: 16-41%), respectively. The 2-year cumulative incidence of LF was 30% (95% CI: 23-41%). Univariate associates with OS included patient age ≥60 years, bone metastasis, increasing tumor size, KRAS mutation, and combined KRAS and TP53 mutation, while increasing tumor size, bone metastasis, biologically effective dose <100 Gy, and combined KRAS and TP53 mutation were associated with LF. Multivariate associates with OS included patient age ≥60 years (HR: 2.4, 95% CI: 1.2-4.8, p = 0.01), lesion size per 1 cm (HR: 1.3, 95% CI: 1.1-1.5, p < 0.01), and KRAS mutation (HR: 2.2, 95% CI: 1.2-4.3, p < 0.01), while no multivariable model for LF retained more than a single variable.

Conclusion: Genomic factors, in particular KRAS and TP53 mutation, may assist in patient selection and radiotherapeutic decision-making for patients with oligometastatic CRC. Prospective validation, ideally with genomic correlation of all irradiated metastases, is warranted.